Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma

Rao, Soumya AM and Santosh, Vani and Somasundaram, Kumaravel (2010) Genome-wide expression profiling identifies deregulated miRNAs in malignant astrocytoma. In: Modern Pathology, 23 (10). pp. 1404-1417.

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Abstract

Malignant astrocytoma includes anaplastic astrocytoma (grade III) and glioblastoma (grade IV). Among them, glioblastoma is the most common primary brain tumor with dismal responses to all therapeutic modalities. We performed a large-scale, genome-wide microRNA (miRNA) (n=756) expression profiling of 26 glioblastoma, 13 anaplastic astrocytoma and 7 normal brain samples with an aim to find deregulated miRNA in malignant astrocytoma. We identified several differentially regulated miRNAs between these groups, which could differentiate glioma grades and normal brain as recognized by PCA. More importantly, we identified a most discriminatory 23-miRNA expression signature, by using PAM, which precisely distinguished glioblastoma from anaplastic astrocytoma with an accuracy of 95%. The differential expression pattern of nine miRNAs was further validated by real-time RT-PCR on an independent set of malignant astrocytomas (n-72) and normal samples (n=7). Inhibition of two glioblastoma-upregulated miRNAs (miR-21 and miR-23a) and exogenous overexpression of two glioblastoma-downregulated miRNAs (miR-218 and miR-219-5p) resulted in reduced soft agar colony formation but showed varying effects on cell proliferation and chemosensitivity. Thus we have identified the miRNA expression signature for malignant astrocytoma, in particular glioblastoma, and showed the miRNA involvement and their importance in astrocytoma development. Modern Pathology (2010) 23, 1404-1417; doi:10.1038/modpathol.2010.135; published online 13 August 2010

Item Type:	Journal Article
Publication:	Modern Pathology
Publisher:	Nature Publishing Group
Additional Information:	Copyright of this article belongs to Nature Publishing Group.
Keywords:	Astrocytoma; glioblastoma; glioma; microarray; microRNA; PAM.
Department/Centre:	Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited:	26 Oct 2010 06:51
Last Modified:	02 Nov 2010 05:45
URI:	http://eprints.iisc.ac.in/id/eprint/33407

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